Bmi-1-RING1B prevents GATA4-dependent senescence-associated pathological cardiac hypertrophy by promoting autophagic degradation of GATA4.

ABSTRACT:

Aims

Senescence-associated pathological cardiac hypertrophy (SA-PCH) is associated with upregulation of foetal genes, fibrosis, senescence-associated secretory phenotype (SASP), cardiac dysfunction and increased morbidity and mortality. Therefore, we conducted experiments to investigate whether GATA4 accumulation induces SA-PCH, and whether Bmi-1-RING1B promotes GATA4 ubiquitination and its selective autophagic degradation to prevent SA-PCH.

Methods and results

Bmi-1-deficient (Bmi-1^-/- ), transgenic Bmi-1 overexpressing (Bmi-1^Tg ) and wild-type (WT) mice were infused with angiotensin II (Ang II) to stimulate the development of SA-PCH. Through bioinformatics analysis with RNA sequencing data from cardiac tissues, we found that Bmi-1-RING1B and autophagy

SUBMITTER: Chen H 

PROVIDER: S-EPMC8989148 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature